Nerve gas poisons are organic esters of substituted phosphoric acids. They inhibit cholinesterase enzymes and therefore are classified as anticholinesterase agents. Three active agents include Tabun (ethyl phosphorodimethylamidocyanidate--((CH.sub.3).sub.2 N)P(O)(CN)OC.sub.2 H.sub.5 --GA), Sarin (isopropyl methylphosphonofluoridate--CH.sub.3 P(O)(F)OCH(CH.sub.3).sub.2 --GB) and Soman (pinocolyl methylphosphonofluoridate--CH.sub.3 P(O)(F)OCH(CH.sub.3)C(CH.sub.3).sub.3 --GD). These compounds are highly volatile and easily disseminated in vapor form. They are readily absorbed through the lungs and eyes, and also the skin and intestinal tract without producing any irritation or other sensation. They are sufficiently potent that even brief exposure may be fatal. Depending on the concentration of the poison, death may occur in as little as one minute, or it may be delayed for 1-2 hours.
Another category of such agents is the V agents, which are more potent, including VX.
Chemically related insecticides include parathion, methyl parathion and malathion, and these exhibit similar toxicity, although they are generally less potent.
Known treatments for these agents include medications which are administered after exposure to the poisons, such as atropine. Prophylactic agents have been investigated, but, in spite of intensive research, only a small number of agents have been identified which offer effective and safe protection against these agents.
Published German Patent Application DE 28 21 778 discloses a prophylactic antidote for organophosphorus pesticides which protects agricultural workers against lethal pesticides during the course of one workday. The agent administered includes hyoscine butyl bromate, a propanol chlorhydrate, dimethyl-carbamoxy-phenyl-trimethyl ammonium bromate and ephedrine. Leadbeater et al, Fundamental and Applied Toxicology Vol. 5, pages S225-S231 (1985) disclose a prophylactic pre-treatment comprising an injection with a carbamate and anti-cholinergic drugs such as Aprophene (2-diethyl-aminoethyl-.alpha.-.alpha.-diphenylpropionate), Hyoscine, Adiphenine, Caramiphen, Dicyclomine and G 3063 (N-methyl-4-pipyridinyl phenylcyclopentanecarboxylate). Carbamates which are mentioned included pyridostigmine and physostigmine. The authors also demonstrated the combined effect of pretreatment with pyridostigmine or physostigmine, with and without Atrophen and post-treatment with a variety of other medications (atropine, P2S and diazepam).
There is a need for more effective prophylactic pre-treatments for the foregoing toxic agents. It is desirable to protect against twice the toxic dose, since this is thought to be the maximum possible field concentration. It is desirable that the treatment be administered orally, rather than by injection, that it provide protection for a long time, 10-12 hours, and that treatment can be repeated during an extended period of time, for example 5 days (10 doses) without severely diminishing the patients ability to function or fight in a combat environment.